Vascular Endothelial Regulation of Obesity-Associated Insulin Resistance

Manna Li, Ming Qian, Jian Xu, Manna Li, Ming Qian, Jian Xu

Abstract

Obesity is a worldwide epidemic that predisposes individuals to metabolic complications, such as type 2 diabetes mellitus and non-alcoholic fatty liver disease, all of which are related to an imbalance between food intake and energy expenditure. Identification of the pathogenic molecular mechanisms and effective therapeutic approaches are urgently needed. A well-accepted paradigm is that crosstalk between organs/tissues contributes to diseases. Endothelial dysfunction characterizes metabolic disorders and the related vascular complications. Over the past two decades, overwhelming studies have focused on mechanisms that lead to endothelial dysfunction. New investigations, however, have begun to appreciate the opposite direction of the crosstalk: endothelial regulation of metabolism, although the underlying mechanisms remain to be elucidated. This review summarizes the evidence that supports the concept of endothelial regulation of obesity and the associated insulin resistance in fat, liver, and skeletal muscles, the classic targets of insulin. Outstanding questions and future research directions are highlighted. Identification of the mechanisms of vascular endothelial regulation of metabolism may offer strategies for prevention and treatment of obesity and the related metabolic complications.

Keywords: adipose; diabetes; endothelial function; insulin resistance; liver; metabolism; obesity; skeletal muscle.

Figures

Figure 1
Figure 1
Endothelial regulation of obesity-associated insulin resistance in fat, skeletal muscle, and the liver. While direct interaction with ECs or EC-derived factors is expected to be shared by the classic targets of insulin, the other regulatory mechanisms could be tissue dependent. The preference in mode of action may reflect the distinct role of each organ/tissue in whole-body metabolism and the heterogeneity of the residing ECs. ECs, endothelial cells; miRNA, microRNA; AdTs, adipose tissues; SkM, skeletal muscle.

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